RU2697392C1 - Method of predicting progression of hiv infection in patients receiving antiretroviral therapy - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, namely immunology, and enables predicting the progression of HIV infection in the patients receiving the antiretroviral therapy. That is ensured by determining a complex of immunological indices by a solid-phase enzyme immunoassay. Concentration of lipopolysaccharide-binding protein (LBP), the level of key pro-inflammatory cytokines: INF-γ, INF-α, IL-6. Using flow cytometry, percentage of activated cells with phenotype: CD3+/CD8+/CD38+/HLA-DR. Critical values of the levels of the above indicators are assigned points: increasing the level of LBP from 55.1 to 80.0 mcg/ml corresponds to 1 point; from 80.1 mcg/ml and higher – 2 points. Increase of INF-γ from 15.1 to 40.0 pg/ml corresponds to 1 point; from 40.1 pg/ml and higher – 2 points. Increase of INF-α from 9.1 to 15.0 pg/ml corresponds to 1 point; from 15.1 pg/ml and higher – 2 points. Increase in IL-6 concentration in excess of 10.1 pg/ml is estimated as 1 point. Percentage of CD3+/CD8+/CD38+/HLA-DR exceeds 22.4 % corresponds to 1 point. That is followed by calculating the total inflammatory coefficient Kv equal to the sum of each index. If Kv is equal to 1 to 3 points, a low risk of progressing HIV infection is determined. If Kv is 4 or more, a high risk of progressing HIV infection is predicted.EFFECT: invention provides more accurate prediction of the progression of HIV infection on the basis of assessing the probability of developing a systemic inflammation in the patient, which reduces the immunological effectiveness of the antiretroviral therapy.1 cl, 9 dwg, 6 tbl, 3 ex

Description

The present invention relates to medicine, namely to infectious diseases, and is intended to select a treatment tactic depending on the activity of systemic inflammation and activation of the immune system.

HIV infection continues to be one of the urgent health problems, due to its intense prevalence. Since 1981, the global HIV pandemic has claimed the lives of more than 35.4 million people and about 36.9 million are currently infected with HIV [1]. In Russia, the spread of HIV infection also continues. According to the Federal Scientific and Methodological Center for the Prevention and Control of AIDS, as of 01.01.2019, 1,326,239 cases of HIV infection were registered among Russian citizens. Of these, 24.0% of HIV-infected people died for various reasons. The spread of HIV infection continues in the Southern and North Caucasian Federal Districts (Southern Federal District and North Caucasian Federal District).

HIV infection remains an incurable disease, however, the use of antiretroviral therapy (ARVT) can significantly reduce its negative medical and socio-economic consequences: stop the progression of the disease, achieve its controlled course, increase the life expectancy of patients with HIV infection and improve its quality, increase the number of births of healthy children.

Despite a thirty-year history of the pandemic and a huge number of studies on HIV infection, the pathogenesis of the disease is not fully understood. ARVT for HIV infection by suppressing viral replication restores the function of the immune system, reduces the risk of developing opportunistic diseases, but does not restore full health and is not always combined with the absence of clinical manifestations of the disease [2]. Even after several years of effective treatment, a significant proportion of patients show immunological disorders, residual HIV viremia, increased markers of activation of the immune system and systemic inflammation [3, 4, 5, 6]. Of particular relevance from the standpoint of research is the fact that the life expectancy of HIV-infected people remains less than that in the general population, which indicates the presence of additional, uncontrolled ART, mechanisms that accelerate death. Patients with HIV infection have an increased risk of developing cardiovascular diseases, diseases of the liver, kidneys, bones and neurological disorders [7, 8, 9].

In this regard, the role of microbial translocation, excessive activity of the immune system, including reactions of chronic inflammation, in the pathogenesis of HIV infection was studied [10, 11, 12]. However, methods for diagnosing, treating, and preventing endotoxinemia as a marker of inflammation are little used in medical practice, which is due to a number of reasons, including insufficient knowledge of the role of endotoxin in human physiology and pathology. At the same time, the determination of the levels of various markers of inflammation is carried out in most clinical laboratories and their cost is low. However, no modern guidelines, including Russian clinical protocols for the provision of medical care for patients with HIV infection, contain recommendations on the practical use of laboratory monitoring of endotoxinemia markers, systemic inflammation, and immune activation.

According to various studies, the prevalence rate of immunological failure of ART is from 7.0% to 19.7% with a tendency to increase in recent years [13]. Currently, a number of methods for assessing the prognosis of HIV infection are known. One of them is based on clinical signs, determining the stages and phases of the disease based on the clinical classification proposed by V.I. Pokrovsky [14, 15]. This method is characterized by subjectivity and a high risk of underdiagnosis, since HIV infection has a very long latent stage of the disease, when there are no clinical signs in most cases.

More objective is the method for determining the course of HIV infection, based on the classification, which is based on the absolute content of CD4 + T-lymphocytes in peripheral blood (SDS / WHO, 2006-2007) [16]. This method takes into account clinical and immunological criteria, but it is not very accurate in predicting the course of HIV infection.

Also, based on an immunological blood test, a forecast option was proposed by determining the quantitative content of CD4 + -, CD8 + -, CD16 + -, CD20 + - lymphocytes and circulating immune complexes (CIC) in patients with HIV infection. (RU 2306566, IPC G01N 33/53, published September 20, 2007) [17]. Exceeding certain levels of CD8 and CD16 according to the authors allows with a probability of 95.5% to predict the rapid course of the disease. The disadvantage of this method is that it was developed before the widespread introduction of ART and does not take into account the effect of ART on the course of HIV infection. In patients with ARVT, in some cases, a delayed reaction from the side of CD4 + lymphocytes is observed, which does not allow to properly assess the prognosis of treatment at the time of studying the immunogram indices.

High production of pro-inflammatory cytokines, called the “cytokine storm”, occurs in response to virus replication [18]. Given virologic efficacy with complete suppression of HIV RNA replication during antiretroviral therapy, it is possible to reduce the pro-inflammatory response, but it continues to be elevated in most patients.

Another method for predicting the course of HIV infection (No. 2097766, MNC G01N 33/49, dated November 27, 1997) is to study the patient’s peripheral blood in order to isolate the genetic material of viruses from the Herpesviridae group [19]. If two or more herpes viruses are detected, a severe course of the disease is predicted. The disadvantages of this method are its complexity, conducting an indirect assessment of the course of the disease. It is based only on the qualitative identification of the genetic material of herpes virus infections, which is only indirect evidence of the activity of the infectious process. The method does not take into account the clinical data of patients and causal relationships of the development of an infectious disease.

A method based on complaints (loss of appetite), clinical data (presence or absence of cough, muscle pain) and liver size measurement is known from the patent literature [20]. Based on the calculation of the value of the prognostic index (K) according to the proposed formula, the authors propose to determine the degree of risk of disease progression. This method is easy to use, but does not imply an assessment of immunological disorders in patients with HIV infection. In addition, this method takes into account subjective indicators (patient complaints) and an objective parameter (liver size), which may be due to concomitant liver diseases.

A method was also found for determining the progression of HIV infection, based on the measurement by ELISA of the level of antibodies to the 3S peptide with the sequence SEQ ID No. 2 [21]. The authors determined the cut-off value of the level of antibodies to the 3S-peptide between patients with an unfavorable and favorable prognosis. When interpreting the results of the prognosis, it is proposed to take into account three independent markers for predicting HIV infection: the level of CD4, HIV viral load, and anti-3S antibodies. The disadvantages of the method are the technical complexity and low availability of determining the concentration of antibodies to the 3S peptide in most laboratories.

The closest analogue to the present invention is a method for predicting the effectiveness of antiretroviral therapy for HIV infection, based on determining the concentration of TNF and IL-6 cytokines by enzyme-linked immunosorbent assay (RU 2414858, published 03/27/2011) [22]. At certain levels of soluble receptors for proteins 55 and 75, tumor necrosis factor alpha (TNF-a) and soluble interleukin-6 receptor (IL-6), a favorable clinical course of HIV infection is predicted 1-3 months after the start of antiretroviral therapy. The disadvantage of this method is the low reliability of the forecast results, since it takes into account a limited number of indicators.

Also, a significant drawback of all of the above methods can be considered the absence of any recommendations on the organization of dispensary observation and optimization of HIV infection therapy based on the prognosis of disease progression.

To address the above disadvantages, the authors propose a method for predicting the progression of HIV infection based on changes in the concentration of lipopolysaccharide-binding protein (LBP), which is a marker of anti-endotoxin protection, as well as changes in the level of key pro-inflammatory cytokines (INF-γ, INF-α, IL-6) and the percentage of activated cells with the phenotype CD3 + / CD8 + / CD38 + / HLA-DR. The objective of the invention is the development of a method for predicting the progression of HIV infection based on a comprehensive assessment of markers of endotoxinemia, systemic inflammation and activation of the immune system.

The technical result is to increase the accuracy of prediction of the progression of HIV infection based on an assessment of the probability of a patient developing systemic inflammation, which reduces the immunological effectiveness of antiretroviral therapy.

The technical result is achieved in that a method for predicting the progression of HIV infection in patients receiving antiretroviral therapy involves determining a complex of immunological parameters by enzyme-linked immunosorbent assay.

In accordance with the invention, the concentration of lipopolysaccharide-binding protein (LBP), the level of key pro-inflammatory cytokines: INF-γ, INF-α, IL-6, and the percentage of activated cells with phenotype: CD3 + were determined by flow cytometry using the above method. / CD8 + / CD38 + / HLA-DR; critical values of the levels of the above indicators are assigned points:

- an increase in LBP level from 55.1 to 80.0 μg / ml corresponds to 1 point; from 80.1 μg / ml and above - 2 points;

- an increase in the level of INF-γ from 15.1 to 40.0 pg / ml corresponds to 1 point; from 40.1 pg / ml and above - 2 points;

- an increase in the level of INF-α from 9.1 to 15.0 pg / ml corresponds to 1 point; from 15.1 pg / ml and above - 2 points;

- an increase in the level of IL-6 concentration above 10.1 pg / ml is estimated at 1 point;

- the percentage of CD3 + / CD8 + / CD38 + / HLA-DR over 22.4% corresponds to 1 point;

then calculate the value of the total inflammatory coefficient Kv equal to the sum of the points for each indicator,

and with a value of Kv equal to from 1 to 3 points, a low risk of progression of HIV infection is determined;

and with a Cv value of 4 or more points, a high risk of HIV progression is predicted.

The proposed method is illustrated by the following materials.

In FIG. Table 1, table 1, shows the levels of markers of systemic inflammation and activation of immunity in the serum of patients with HIV infection (mean values and average error M ± m; pg / ml - picograms per milliliter, μg / ml - micrograms per milliliter ng / ml - nanograms per milliliter).

In FIG. 2 presents table 2, showing the scale of the progression of HIV infection based on the determined parameters.

In FIG. 3 is a table 3 showing the likelihood of rapid progression of HIV infection (P).

In FIG. 4 - table 4, showing the dynamics of the main laboratory parameters of patient F.

In FIG. 5 - table 5, showing the dynamics of the main laboratory parameters of patient P.

In FIG. 6 - table 6, showing the dynamics of the main laboratory parameters of patient B.

In FIG. 7 is a graph of the change in the ROC curve of the LBP.

In FIG. Figure 8 shows a graph of the ROC curve of INF-γ.

In FIG. 9 is a graph of the ROC curve of INF-α.

The essence of the method consists in the fact that 10 ml of venous blood is taken from patients (with a sterile syringe from the ulnar vein by venipuncture in the morning on an empty stomach) and the concentration of the anti-endotoxin defense marker (LBP) and the level of pro-inflammatory cytokines (INF-γ) are determined in it by means of enzyme-linked immunosorbent assay , INF-α and IL-6), as well as by the method of flow cytometry determine the percentage of activated cells with the phenotype CD3 + / CD8 + / CD38 + / HLA-DR. Based on the results, in accordance with the proposed methodology, the total inflammatory coefficient (Sv) is calculated and the likelihood of developing rapid progression of HIV infection (P) is determined.

The advantages of the method are accessibility, non-invasiveness, high accuracy, the absence of a threat to the health of the patient, the ability to quickly determine the prognostic risk in patients with HIV infection in the early stages.

A rapid progression of HIV infection is considered to be a variant of the course when, after a year of ART, it is not possible to increase the absolute number of CD4 + T-lymphocytes above 350 cells per microliter (cells per μl), there is no or insufficient growth of CD4 + T-lymphocytes (less than 50 cells per year) and / or the patient goes into a more severe clinical stage of the disease. A slowly progressive course of the disease is considered to be the option of developing HIV infection, when for more than 12 months of ART, the level of CD4 + T-lymphocytes remains above 350 cells. in μl, there is no negative dynamics in the absolute number of CD4 + T cells and the patient’s disease remains in the same clinical stage. In the proposed method, it is possible to determine the prognosis of disease progression after 6 months of ART and optimize patient management tactics in accordance with the forecast.

Under our supervision, there were 162 patients with HIV infection. The average age of patients was 39.4 ± 8.2 years. The study included male and female HIV-infected patients over 18 years of age at all stages of the disease, receiving ARVT for more than 6 months. Exclusion criteria were: use of psychotropic and narcotic drugs during the last 6 months, pregnancy, the presence of acute or exacerbation of chronic somatic diseases. In most patients, the stage of secondary diseases 4A was diagnosed - 49.4%. Subclinical stage (stage 3) was established in 30.2% of patients, stage 4B - 17.9%, 4B - 2.5%. ART was carried out in accordance with the recommendations adopted in the Russian Federation. The duration of ART was 5.1 ± 2.2 years; the patient observation range was 5.4 ± 2.1 years.

The main target cells for HIV infection are CD4 lymphocytes. Their level underlies the classification of HIV infection by CDC (1993) and Walter Reed (2000).

Rapid rates of disease progression were observed if, despite ARVT, the level of CD4 + T-lymphocytes during 6 months of therapy was less than 350 cells. in μl, slow pace, if within 6 months of therapy the level of CD4 was more than 350 cells. in μl.

The effect of CD8 + T-lymphocyte function on the progression of HIV infection is of significant interest, since cytotoxic T-lymphocytes are the main effector cells of a specific cellular immune response. HIV-specific CD8 + T cells play a crucial role in the fight against HIV replication and express CD38 and HLA-DR markers under enhanced immune activation. The severity of immune activation is an additional predictive marker of the progression of HIV infection, and therefore, when predicting the course of the disease, the percentage of T cells with the CD3 + / CD8 + / CD38 + / HLA-DR phenotype (%) should be taken into account.

In our study, patients with HIV infection were formed in 2 groups depending on the rate of progression of HIV infection, which was determined on the basis of CD4 values after 6 months of ART: group 1 - CD4 level less than 350 cells. in mcl., 2nd group - more than 350 cells. in μl.

In group 1 patients with a CD4 level of less than 350 cells. in μl., the following indicators were found at a significantly higher concentration level: LBP, IL6, INF-γ, INF-α and the proportion of activated lymphocytes with the CD3 + / CD8 + / CD38 + / HLA-DR phenotype (p <0.05), tab. 1. Therefore, they were chosen as the main markers of the proposed prognostic method.

The results of the study were processed by the statistical program SPSS Statistics Base 22.0 using binary logistic regression (ROC analysis), which allows to determine the probability of an event, as well as the sensitivity and specificity of the method.

The ROC analysis showed that to predict the progression of HIV infection, it is advisable to determine the level of concentration of LBP and INF-γ, as well as INF-α in the blood. With an increase in the level of LBP, it is possible to predict the progression of HIV infection with a criterion value of 55.1 to 80 μg / ml with a probability of 86.7%. An LBP of 80.1 μg / ml or higher indicates a 96.2% chance of a rapid progression of HIV infection.

According to the results of constructing the ROC curve of the LBP (see the graph in Fig. 7) using the method of binary logistic regression, the probability of rapid progression of HIV infection was 90.3% (AUC = 0.903), with a sensitivity of 86.96% and a specificity of 93 ,18%

When the concentration of INF-γ in the blood is from 15.1 to 40.0 pg / ml, the progression of HIV infection can be predicted with a probability of 91.7%. An increase in the concentration of INF-γ in the blood to a level of 40.1 pg / ml and above also indicates a 95.5% probability of rapid progression of HIV infection. According to the results of constructing the INF-γ ROC curve using the binary logistic regression method, the probability of developing HIV infection progression was 83.6% (AUC = 0.836), the method sensitivity was 88.00% and the specificity was 76.3% (see graph on Fig. 8).

с использованием метода бинарной логистической регрессии, вероятность развития прогрессирования ВИЧ-инфекции составила 86,1% (AUC=0,861), чувствительность метода 78,57% и специфичностью 83,33% (см. график на фиг. 9).With an increase in the level of INF-α in the blood from 9.1 pg / ml to 15.0 pg / ml, progression of HIV infection can be predicted with a probability of 83.3%. Its increase to 15.1 pg / ml or more also indicates a 95.7% probability of rapid progression of HIV infection. According to the results of constructing the ROC curve

using the method of binary logistic regression, the probability of progression of HIV infection was 86.1% (AUC = 0.861), the sensitivity of the method was 78.57% and the specificity of 83.33% (see graph in Fig. 9).

The inventive method for predicting the progression of the disease in patients with HIV infection is as follows. 6 months after initiation of ART in HIV patients, in addition to the standard serum examination, serum levels of LBP, INF-γ, INF-α, IL-6 and the percentage of T cells with the CD3 + / CD8 + / CD38 + / HLA-DR phenotype are determined .

Next, HIV progression scores were determined. An increase in LBP level from 55.0 to 80.0 μg / ml corresponds to 1 point of risk of progression of HIV infection, from 80.1 μg / ml and above - 2 points. An increase in the level of INF-γ from 15.0 to 40.0 pg / ml and from 40.1 pg / ml and higher also corresponds to 1 and 2 points.

An increase in the level of INF-α from 9.0 to 15.0 pg / ml and from 15.1 pg / ml and higher also corresponds to 1 and 2 points. The IL-6 concentration level (10.1 pg / ml and higher) corresponded to 1 point, the percentage of CD3 + / CD8 + / CD38 + / HLA-DR - 22.4% and higher was regarded as 1 point, see table. 2.

A low risk of rapid progression of HIV infection was determined when the values of the total inflammatory coefficient Kv from 1 to 3. Values of 4 or more, this risk can be considered high. If a high risk of progression of HIV infection is identified, the patient needs a more frequent clinical examination and a decision on the modification of the ARVT regimen with the appointment of drugs with high immunological efficacy and with a maximum genetic barrier to the formation of HIV resistance to ARVT. See table 3

Thus, in the course of the study, a technique was obtained that with high accuracy allows predicting the course of HIV infection during ART and in the early stages can determine the risk of progression of the disease. It is assumed that the use of this method will help doctors in time choose the appropriate treatment tactics for patients with unfavorable prognostic risk, preventing the implementation of a negative prognosis.

The use of the method is illustrated by a clinical example.

Patient F., 32 years old. She has been registered at the State Budget Institution of Healthcare in the Rostov Region as the Center for the Prevention and Control of AIDS (GBU RO “CP and B with AIDS”) since 2007 (HIV immune blot positive from 19.01.2007). Diagnosis from 02/19/2019: HIV infection, stage of secondary diseases (IVA), remission phase in the presence of ART. He has been receiving ART since January 2018 under the TDF + 3TC + EFV scheme. The level of adherence to antiretroviral therapy is rated as high, drug tolerance is good. During 2018, the patient visited the AIDS Clinical Hospital nine times with the goal of follow-up and receiving ART. The level of CD4 + T cells at the beginning of ART was 15% 270 cells per µl .; CD8 + T cells - 70% of 1258 cells per μl .; IRI - 0.21. The level of HIV viral load from 12/26/2017 is 115,000 copies / ml. The dynamics of the main laboratory parameters of patient F. are presented in table. four.

When determining the prognosis of the immunological effectiveness of antiretroviral therapy after 6 months. The following data were obtained for ART: LBP - 45 μg / ml, INF-γ - 27 pg / ml, INF-α - 12 pg / ml, IL6 - 9 pg / ml,% CD3 + / CD8 + / CD38 + / HLA-DR - 17 % The total inflammatory coefficient (Sv) is 2. The likelihood of progression of HIV infection (P) is low. It is advisable to continue ART according to the accepted scheme.

Patient P., 46 years old. Member of the dispensary registration at the State Budget Institution of Health of the Rostov Region “Center for the Prevention and Control of AIDS” (GBU RO “CP and B with AIDS”) since 2005 (HIV immune blot positive from 05.05.2005). The diagnosis of February 19, 2019: HIV infection, the stage of secondary diseases (IVB), the remission phase against ART. Recurrent oropharyngeal candidiasis without exacerbation, recurrent viral-bacterial infection (including HSV + CMV), HIV encephalopathy, 10% body mass deficiency, chronic bronchitis without exacerbation. She has been receiving ART since 2006 under the TDF + ABC + LPV / r scheme. At the beginning of 2015, a virological treatment failure was recorded and in April 2015, based on a study of HIV resistance to ARVP, the treatment regimen was changed to TDF + ABC + RAL. The level of adherence to antiretroviral therapy is rated as high, drug tolerance is good. During 2018, the patient visited the AIDS Clinical Hospital eight times for the purpose of follow-up and receiving ART. The level of CD4 + T cells at the beginning of ART was 10% 170 cells per μl, CD8 + T cells 47% 781 cells per μl, and IRI 0.21. The level of HIV viral load from 12/26/2017 is 3,639 copies / ml. The dynamics of the main laboratory parameters of patient P. are presented in table. five.

When determining the prognosis of the immunological effectiveness of antiretroviral therapy, the following data were obtained: LBP - 118 μg / ml, INF-γ - 48.8 pg / ml, INF-α - 14 pg / ml, IL6 - 13.1 pg / ml,% CD3 + / CD8 + / CD38 + / HLA-DR - 23%. The total inflammatory coefficient (Sv) is 7. The probability of developing rapid progression of HIV infection (P) is high. Such a patient is shown to increase the frequency of the clinical examination in order to timely detect secondary diseases and to modify the ART regimen.

Patient B., 52 years old. She has been registered in the State Budget Institution of Health of the Rostov Region as a Center for the Prevention and Control of AIDS (GBU RO "C&S with AIDS") since 2001 (HIV immune blot positive from 08.06.2001). Diagnosis from 02/19/2019: HIV infection, stage of secondary diseases (IVA), remission phase in the presence of ART. Recurrent viral-bacterial infection (including HSV + CMV), HIV encephalopathy. Chronic hepatitis C (HCV RNA PCR negative). She has been receiving ART since March 2015 under the scheme ABC + 3TC + DRV / r. The level of adherence to antiretroviral therapy is rated as high, drug tolerance is good. During 2018, the patient visited the AIDS Clinical Hospital ten times with the goal of follow-up and receiving ART. The level of CD4 + T cells at the beginning of ART was 38% 471 cells per μl, CD8 + T cells - 33% 407 cells per μl, IRI 1.16. The level of HIV viral load from 03/20/15 was 992,000 copies / ml. The dynamics of the main laboratory parameters of patient B. are presented in table. 6.

When determining the prognosis of the immunological effectiveness of antiretroviral therapy after 6 months. ART The following data were obtained: LBP - 50 μg / ml, INF-γ - 6.1 pg / ml, INF-α - 9.8 pg / ml, IL6 - 4.2 pg / ml,% CD3 + / CD8 + / CD38 + / HLA-DR - 7.9%. The total inflammatory coefficient (Sv) is 1. The likelihood of progression of HIV infection (P) is low. It is advisable to continue ART according to the accepted scheme.

According to our proposed method, we give the calculations of sensitivity, specificity and prognostic value of a positive result.

Sensitivity = а / (а + с) ⋅100%;

specificity = d / (b + d) ⋅100%;

predictive value = a / (a + b) ⋅100%, where

a - patients with HIV infection, the rapid progression of the disease in which is detected using the proposed method (truly positive),

b - patients with HIV infection who were predicted, but did not have a rapid progression of the disease (false positive),

c - patients whose rapid progression of HIV infection could not be predicted using a test (false negative),

d - HIV-infected patients with a negative test result who did not have a rapid progression of the disease (genuinely negative)

Sensitivity = a / (a + s) ⋅100 = 98 / (98 + 9) ⋅100% = 91.59%

Specificity = d / (d + b) ⋅100% = 49 / (49 + 6) ⋅100% = 89.09%

Predictive value = a / (a + b) ⋅100% = 98 / (98 + 6) ⋅100% = 94.23%

Thus, the sensitivity of the proposed method for predicting the progression of HIV infection was 91.59%, specificity 89.09%, the prognostic value of a positive result was 94.23%.

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Claims (9)

A method for predicting the progression of HIV infection in patients receiving antiretroviral therapy, including determining the complex of immunological parameters by enzyme-linked immunosorbent assay, characterized in that the concentration of lipopolysaccharide-binding protein (LBP), the level of key pro-inflammatory cytokines were determined using the above method: INF-γ, INF-α, IL-6, as well as the method of flow cytometry, the percentage of activated cells with the phenotype was determined: CD3 + / CD8 + / CD38 + / HLA-DR; critical values of the levels of the above indicators are assigned points: - an increase in LBP level from 55.1 to 80.0 μg / ml corresponds to 1 point; from 80.1 μg / ml and above - 2 points; - an increase in the level of INF-γ from 15.1 to 40.0 pg / ml corresponds to 1 point; from 40.1 pg / ml and above - 2 points; - an increase in the level of INF-α from 9.1 to 15.0 pg / ml corresponds to 1 point; from 15.1 pg / ml and above - 2 points - an increase in the level of IL-6 concentration above 10.1 pg / ml is estimated at 1 point; - the percentage of CD3 + / CD8 + / CD38 + / HLA-DR over 22.4% corresponds to 1 point; then calculate the value of the total inflammatory coefficient Kv equal to the sum of the points for each indicator, and with a value of Kv equal to from 1 to 3 points, a low risk of progression of HIV infection is determined; and with a Cv value of 4 or more points, a high risk of HIV progression is predicted.

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